Airway epithelial cells express receptors for the proinflammatory cytokines TNF-alpha and IL-1beta. Cells may modulate cytokine responses by the alteration of cellular receptor numbers or affinity. Airway epithelial cells express the P55 TNFalpha receptor. Protein Kinase C activation by phorbol ester in a human epithelial cell line or in human airway epithelial cells in primary culture results in the solubilization of cell surface P55 TNFalpha receptors. Similarly IL-1beta treatment of airway epithelial cells induces the shedding of TNFalpha P55 receptors. This effect is inhibited by pretreatment of the cells with the PKC antagonist calphostin C. Conversely, dexamethasone treatment of epithelial cells results in an increase in cell associated TNFalpha receptor protein and in a reduction of TNFalpha receptor shedding. One manuscript has been prepared and studies are in progress to investigate the mechanisms of PKC induced TNFalpha receptor shedding as well as other mechanisms of epithelial cell modulation of cytokine responses. A knowledge of the mechanisms by which epithelial cells may modulate responses to inflammatory cytokines may allow for new therapeutic approaches to the reduction of airway inflammation.